The proposed research aims to develop the mouse tumor system as an experimental model for cancer immunotherapy, to reveal fundamental aspects of antitumor immunity, and to indicate effective and hazardous immunotherapeutic procedures. Areas of investigation are primarily four: 1. To determine the effect on host resistance of immunotherapy in autochthonous and syngeneic hosts at different stages of progressive disease and at different times relative to surgery and radiotherapy. The tests will use nonliving tumor cell preparations, macrophage preparations, and bacterial immuno-potentiators. 2. To study the conditions and procedures which may increase or reduce the risk of specific depression of host resistance by excess free tumor antigen or blocking factors. 3. To determine the strength and the frequency of occurrence of specific antigens, presumably not virion or virion-associated, in tumors arising spontaneously in mammary tumor virus (MTV)-free C2Hf/He mice. To determine the frequency and variability of antigens in different tumors arising from a single line of preneoplastic tissue transplanted into C3Hf/He mice. 4. To determine the cause of the enhanced growth of syngeneic mammary tumors transplanted into immunized mice of the C3H/Ki subline. The assay system will use in vivo sensitization and challenge methods. The challenge will use s.c. implantation and will also select and use C3Hf/He tumors which metastasize spontaneously in sublethally irradiated, intramuscularly implanted mice, to study immune factors under conditions simulating metastatic spread of tumor growth.